The Journal of Organic Chemistry
Note
(E)-Ethyl 4-(2-Bromo-3,4-dimethoxyphenyl)but-2-enoate
(1d). Yield: 82% (1.35g, 4.101 mmol); colorless oil; IR (CHCl3,
cm−1) υmax 895, 978, 1024, 1050, 1142, 1188, 1245, 1276, 1477, 1714,
Na)+] 238.0844, found 238.0836. Anal. Calcd for C13H13NO2: C,
72.54; H, 6.09; N, 6.51. Found: C, 72.46; H, 6.24; N, 6.62.
Ethyl 1-Amino-6-methoxynaphthalene-2-carboxylate (2b).
Yield: 78% (0.191g, 0.778 mmol); gum; IR (CHCl3, cm−1) υmax 870,
1076, 1245, 1340, 1599, 1672, 3346, 3457; 1H NMR (200 MHz,
CDCl3) δ 1.42 (t, J = 7.1 Hz, 3H), 3.92 (s, 3H), 4.36 (q, J = 7.1 Hz,
2H), 6.97 (d, J = 8.8 Hz, 1H), 7.02−7.11 (m, 2H), 7.82 (t, J = 8.8 Hz,
2H); 13C NMR (50 MHz, CDCl3) δ 14.5, 55.2, 60.0, 103.2, 107.0,
115.1, 117.0, 117.9, 123.3, 127.5, 138.3, 148.9, 159.6, 168.8; HRMS
(ESI+) m/z calcd for (C14H15NO3)+ [(M + Na)+] 268.0950, found
268.0944. Anal. Calcd for C14H15NO3: C, 68.56; H, 6.16; N, 5.71.
Found: C, 68.44; H, 5.99; N, 5.49.
Ethyl 1-Amino-6,7-dimethoxynaphthalene-2-carboxylate
(2c). Yield: 74% (0.204g, 0.741 mmol); colorless oil; IR (CHCl3,
cm−1) υmax 798, 865, 964, 1015, 1135, 1157, 1232, 1264, 1471, 1665,
2965, 3335, 3346; 1H NMR (200 MHz, CDCl3) δ 1.42 (t, J = 7.1 Hz,
3H), 4.00 (s, 3H), 4.01 (s, 3H), 4.36 (q, 2H, J = 7.1 Hz), 6.95 (d, J =
8.9 Hz, 1H), 7.02 (s, 1H), 7.05 (s, 1H), 7.77 (d, 1H, J = 8.9 Hz); 13C
NMR (50 MHz, CDCl3) δ 14.4, 55.6 60.1, 101.1, 103.8, 107.1, 114.8,
117.6, 125.1, 132.4, 147.6, 148.6, 150.9, 168.8; HRMS (ESI+) m/z
calcd for (C15H17NO4)+ [(M + Na)+] 298.1055, found 298.1062. Anal.
Calcd for C15H17NO4: C, 65.44; H, 6.22; N, 5.09. Found: C, 65.69; H,
6.18; N, 5.11.
1
2965; H NMR (200 MHz, CDCl3) δ 1.28 (t, J = 7.2 Hz, 3H), 3.61
(dd, J = 1.3, 7.1 Hz, 2H), 3.86 (s, 3H), 3.87 (s, 3H), 4.17 (q, J = 7.2
Hz, 2H), 6.81−7.27 (m, 3H); 13C NMR (50 MHz, CDCl3) δ 14.2,
38.1, 56.0, 60.1, 111.3, 120.3, 125.2, 130.2, 145.8, 146.7, 152.3, 166.2.
Anal. Calcd for C14H17BrO4: C, 51.08; H, 5.21; Br, 24.27. Found: C,
50.98; H, 5.14; Br, 24.32.
(E)-Ethyl 4-(5-(Benzyloxy)-2-bromo-4-methoxyphenyl)but-
2-enoate (1e). Yield: 84% (1.70g, 4.195 mmol); colorless oil; IR
(CHCl3, cm−1) υmax 780, 882, 1035, 1072, 1151, 1190, 1278, 1292,
1456, 1712, 2974; 1H NMR (200 MHz, CDCl3) δ 1.30 (t, J = 7.2 Hz,
3H), 3.27 (dd, J = 1.4, 7.1 Hz, 2H), 3.89 (s, 3H), 4.19 (q, J = 7.2 Hz,
2H), 5.10 (s, 2H), 6.14 (td, J = 7.2, 15.8 Hz, 1H), 7.02 (s, 2H), 7.32−
7.44 (m, 6H); 13C NMR (50 MHz, CDCl3) δ 14.1, 38.1, 55.8, 60.0,
113.0, 114.2,115.5, 122.4, 128.8, 145.5, 148.4, 166.0. Anal. Calcd for
C20H21BrO4: C, 59.27; H, 5.22; Br, 19.72. Found: C, 59.34; H, 5.28;
Br, 19.65.
(E)-Ethyl 4-(2-Bromo-4-nitrophenyl)but-2-enoate (1h). Yield:
84% (1.32g, 4.202 mmol); colorless oil; IR (CHCl3, cm−1) υmax 768,
1
878, 1018, 1085, 1178, 1285, 1298, 1455, 1716, 2960; H NMR (200
MHz, CDCl3) δ 1.27 (t, J = 7.2 Hz, 3H), 3.63 (dd, J = 1.3, 7.1 Hz,
2H), 4.16 (q, J = 7.2 Hz, 2H), 5.74 (td, J = 3.8, 15.7 Hz, 1H), 6.36 (dd,
J = 1.8, 2.9 Hz, 2H), 6.97−7.12 (m, 1H); 13C NMR (50 MHz, CDCl3)
δ 14.2, 38.1, 60.2, 98.0, 105.1, 106.8, 122.7, 139.1, 145.3, 156.9, 159.6,
166.2. Anal. Calcd for C12H12BrNO4: C, 45.88; H, 3.85; Br, 25.44; N,
4.46. Found: C, 45.76; H, 3.76; Br, 25.36; N, 4.39.
Ethyl 1-Amino-7,8-dimethoxynaphthalene-2-carboxylate
(2d). Yield: 73% (0.201g, 0.730 mmol); colorless oil; IR (CHCl3,
1
cm−1) υmax 779, 826, 956, 1018, 1267, 1579, 1672, 3334, 3464; H
NMR (200 MHz, CDCl3) δ 1.41 (t, J = 7.2 Hz, 3H), 3.97 (s, 6H), 4.35
(q, J = 7.2 Hz, 2H), 6.82 (d, J = 10.4 Hz, 1H), 7.24−7.28 (m, 1H),
7.41 (d, J = 9.0 Hz, 1H), 7.69 (d, J = 9.0 Hz, 1H); 13C NMR (50 MHz,
CDCl3) δ 14.5, 56.8, 61.5, 102.7, 114.1, 116.8, 118.0, 124.4, 125.3,
133.2, 147.0, 148.7, 151.1, 168.9; HRMS (ESI+) m/z calcd for
(C15H17NO4)+ [(M + Na)+] 298.1055, found 298.1049. Anal. Calcd
for C15H17NO4: C, 65.44; H, 6.22; N, 5.09. Found: C, 65.35; H, 6.31;
N, 5.12.
Ethyl 4-(2-Bromo-4,5-dimethoxyphenyl)pent-2-enoate (1j).
Yield: 89% (1.53g, 4.458 mmol); colorless oil; IR (CHCl3, cm−1) υmax
1
856, 937, 1030, 1133, 1233, 1268, 1445, 1716,2984; H NMR (200
MHz, CDCl3) δ 1.26 (t, J = 7.2 Hz, 3H), 1.37 (d, J = 7.0 Hz, 3H), 3.85
(s, 3H), 3.86 (s, 3H), 4.06 (qd, J = 5.5, 1.5 Hz, 1H), 4.19 (q, J = 7.2
Hz, 2H), 5.80 (dd, J = 15.79, 1.64 Hz, 1H), 6.63 (s, 1H), 7.01 (s, 1H),
7.09 (dd, J = 15.79, 5.69 Hz, 1H); 13C NMR (50 MHz, CDCl3) δ 14.1,
19.1, 40.1, 55.8, 60.0, 110.6, 113.9, 115.5, 120.4, 134.0, 148.2, 148.7,
150.9, 166.2 Anal. Calcd for C15H19BrO4: C, 52.49; H, 5.58; Br, 23.28.
Found: C, 52.33; H, 5.12; Br, 23.18.
Ethyl 4-(1-Bromonaphthalen-2-yl)but-2-enoate (1k). Yield:
89% (1.49g, 4.458 mmol); yellow oil; IR (CHCl3, cm−1) υmax 758, 872,
1058, 1175, 1184, 1245, 1468, 1713, 2962; 1H NMR (200 MHz,
CDCl3) δ 1.26 (t, J = 7.2 Hz, 3H), 3.89 (dd, J = 6.3, 1.6 Hz, 2H), 4.15
(q, J = 7.2 Hz, 2H), 5.77 (dt, J = 15.6, 1.6 Hz, 1H), 7.06−7.30 (m,
2H), 7.45−7.62 (m, 2H), 7.77 (t, J = 8.5 Hz, 2H), 8.30 (d, J = 8.3 Hz,
1H); 13C NMR (50 MHz, CDCl3) δ 14.3, 39.8, 60.2, 122.9, 124.4,
126.3, 127.4, 127.5, 127.8, 128.0, 128.3, 132.6, 133.5, 135.2, 145.2,
166.1. Anal. Calcd for C16H15BrO2: C, 60.21; H, 4.74; Br, 25.03.
Found: C, 60.11; H, 4.32; Br, 24.90.
General Experimental Procedure for the Preparation of
Substituted Naphthalene Derivatives (2a−k). To a stirred
solution of alkenes 1a−k (1 mmol) in dry DMF (10 mL) was
added CuCN (3 mmol,) and the entire solution was refluxed under N2
for 12 h (monitored by TLC). The reaction mixture was then cooled
to room temperature and diluted with water (20 mL) and EtOAc (15
mL). The organic layer was separated, and the aqueous layer was
extracted with EtOAc (3 × 20 mL). The combined organic extracts
were washed with brine, dried over anhydrous Na2SO4, and
concentrated under reduced pressure to give crude product, which
was purified by column chromatography [silica gel (230−400 mesh)
and petroleum ether/EtOAc (7:3) as an eluent] to give ethyl 1-amino-
2-naphthalene carboxylate derivatives (2a−k) in 73−91% yield.
Ethyl 1-Aminonaphthalene-2-carboxylate (2a). Yield: 85%
(0.183g, 0.850 mmol); gum; IR (CHCl3, cm−1) υmax 798, 865, 964,
1015, 1135, 1157, 1232, 1264, 1471, 1665, 2965, 3335, 3346; 1H NMR
(200 MHz, CDCl3) δ 1.42 (t, J = 7.1 Hz, 3H), 4.37 (q, J = 7.1 Hz,
2H), 7.05 (d, J = 8.9 Hz, 1H), 7.44−7.53 (m, 2H), 7.72 (d, J = 7.8 Hz,
1H), 7.87 (d, J = 8.9 Hz, 2H); 13C NMR (50 MHz, CDCl3) δ 14.4,
60.1, 104.2, 115.7, 121.4, 123.1, 125.0, 126.6, 128.2, 128.4, 136.4,
148.8, 168.8; HRMS (ESI+) m/z calcd for (C13H13NO2)+ [(M +
Ethyl 1-Amino-6-(benzyloxy)-7-methoxynaphthalene-2-car-
boxylate (2e). Yield: 76% (0.267 g, 0.759 mmol); colorless solid; mp
144−145 °C; IR (CHCl3, cm−1) υmax 1247, 1483, 1619, 1676, 3434,
3452; 1H NMR (200 MHz, CDCl3) δ 1.41 (t, J = 7.1 Hz, 3H), 4.00 (s,
3H), 4.35 (q, J = 7.1 Hz, 2H), 5.26 (s, 2H), 6.95 (d, J = 8.8 Hz, 1H),
7.04 (s, 1H), 7.18 (s, 1H), 7.30−7.51 (m, 5H), 7.76 (d, J = 8.8 Hz,
1H); 13C NMR (50 MHz, CDCl3) δ 14.5, 55.8, 60.1, 71.3, 104.3,
107.6, 115.2, 117.9, 125.5, 127.4, 128.1, 128.7, 132.9, 136.7, 147.5,
147.9, 151.8, 168.9; HRMS (ESI+) m/z calcd for (C21H21NO4)+ [(M
+ Na)+] 374.1368, found 374.1375. Anal. Calcd for C21H21NO4: C,
71.78; H, 6.02; N, 3.99. Found: C, 71.66; H, 5.94; N, 4.03.
Ethyl 1-Amino-6-methylnaphthalene-2-carboxylate (2f).
Yield: 81% (0.186g, 0.811 mmol); colorless oil; IR (CHCl3, cm−1)
1
υmax 1078, 1222, 1239, 1257 1605, 1663, 3352, 3453; H NMR (200
MHz, CDCl3) δ 1.43 (t, J = 7.1 Hz, 3H), 2.54 (s, 3H), 4.37 (q, J = 7.1
Hz, 2H), 7.02 (d, J = 8.8 Hz, 1H), 7.37 (d, J = 8.2 Hz, 1H), 7.63 (d, J
= 8.1 Hz, 2H), 7.81 (d, J = 8.8 Hz, 1H); 13C NMR (50 MHz, CDCl3)
δ 14.5, 22.0, 60.2, 104.9, 116.1, 120.9, 123.4, 125.7, 128.4, 130.4, 134.6,
134.9, 147.9, 168.9; HRMS (ESI+) m/z calcd for (C14H15NO2)+ [(M
+ Na)+] 252.1000, found 252.0992. Anal. Calcd for C14H15NO2: C,
73.34; H, 6.59; N, 6.11. Found: C, 73.26; H, 6.52; N, 6.01.
Ethyl 1-Amino-6-fluoronaphthalene-2-carboxylate (2g).
Yield: 88% (0.205g, 0.870 mmol); gum; IR (CHCl3, cm−1) υmax
767, 1249, 1604, 1673, 2987, 3347, 3447; 1H NMR (200 MHz,
CDCl3) δ 1.43 (t, J = 7.2 Hz, 3H), 4.37 (q, J = 7.2 Hz, 2H), 6.99 (d, J
= 8.9 Hz, 1H), 7.15−7.24 (m, 1H), 7.34 (dd, J = 2.5, 7.1 Hz, 1H), 7.86
(d, J = 9.2 Hz, 1H), 7.9 (d, J = 8.9 Hz, 1H); 13C NMR (50 MHz,
CDCl3) δ 14.4, 60.2, 104.1, 111.8 (d, J = 20.8 Hz), 114.7 (d, J = 25.4
Hz), 115.1 (d, J = 3.9 Hz), 120.0, 124.2 (d, J = 10.0 Hz), 128.1, 138.0
(d, J = 9.2 Hz), 148.8, 162.2 (d, J = 249.7 Hz), 168.6; HRMS (ESI+)
m/z calcd for (C13H12FNO2)+ [(M + Na)+] 256.0750, found
256.0743. Anal. Calcd for C13H12FNO2: C, 66.94; H, 5.19; N, 6.01.
Found: C, 67.03; H, 5.13; N, 5.89.
Ethyl 1-Amino-6-nitronaphthalene-2-carboxylate (2h). Yield:
91% (0.237g, 0.911 mmol); Red solid; mp 176−177 °C; IR (CHCl3,
cm−1) υmax 1243, 1345, 1602, 1674, 3352, 3446; 1H NMR (200 MHz,
D
dx.doi.org/10.1021/jo400244h | J. Org. Chem. XXXX, XXX, XXX−XXX